The University of Virginia (UVa) Schools of Medicine and Engineering have established successful research programs in the development and application of imaging methodologies and techniques for non- invasive serial studies of the molecular mechanisms underlying infectious diseases1, 2 heart disease 3-5, lung inflammation 6 and cancer 7, 8 amongst many others in small animals and humans. Imaging is carried out at the UVa Molecular Imaging Center (UVaMIC) that houses state of the art imaging devices including magnetic resonance (MR), X-ray computed tomography (CT), planar fluorescence and bioluminescence imaging (BLI), single gamma emission tomography (SPECT), and positron emission tomography (PET) scanners. Bioluminescence and fluorescence imaging 9-11 have emerged as high sensitivity and high throughput imaging modalities for targeted molecular imaging. We are requesting funds for a next generation high sensitivity and high-resolution small animal optical imager with 3D reconstruction capabilities based on a computational technique called diffuse optical tomography. We propose to purchase the SPECTRUM, small animal fluorescence and bioluminescence optical scanner from Caliper Life Sciences, Inc. The present IVIS 100 scanner from Xenogen (now a part of Caliper Life Sciences, Inc.) has a number of limitations, which would be overcome by the proposed new optical scanner in the UVaMIC. The main benefits of the new system will be better fluorescence imaging and the ability to create 3D images. Full utilization of the enhanced capabilities afforded by the SPECTRUM small animal optical scanner will be assured through an existing comprehensive technical, scientific, and administrative plan. PUBLIC HEALTH RELEVANCE: We are requesting funds for a state of art bioluminescence and fluorescence small animal scanner, which is a necessary resource for the University of Virginia (UVa) program in molecular imaging. Molecular imaging is the "visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems."12 This probing by imaging of biological processes can be used to localize and quantify particular events. Optical imaging is a preferred functional imaging modality over Positron Emission Tomography (PET) or Single Gamma Emission Tomography (SPECT) due to its high sensitivity and throughput. Moreover, molecular events in an animal subject could be non-invasively studied over days due to longer biological half-life as compared to radionuclide imaging where half-life is a major constraint. However, a combination of optical and PET and/or SPECT could enable both high sensitivity and high resolution imaging of molecular events in animal subjects and humans. Although whole body human scanning is unlikely, the feasibility of the diffuse optical tomography technique for imaging breast cancer, superficial sentinel lymph nodes, the brain surface, arms and fingers has been shown. The relevance to public health of the addition of the next generation bioluminescence and fluorescence scanner to the already extensive imaging resources available at UVaMIC is that the presence of this scanner will enable research that is now not possible on new ways of detecting, characterizing, and treating diseases utilizing optical scanning.